Study of TBI-1501 for Relapsed or Refractory Acute Lymphoblastic Leukemia

Phase 1

Active, not recruiting

• Conditions: Lymphoblastic Leukemia, Acute Adult
• Interventions: Biological: TBI-1501

• Registration Number: NCT03155191
• Lead Sponsor: Takara Bio Inc.

Brief Summary

Evaluate the safety (P-I), pharmacokinetics and anti-tumor effect of immunotherapy of autologous T cells genetically modified to express anti-CD19 chimeric antigen receptor (CAR) (TBI-1501) for relapsed or refractory CD19+ B-cell acute lymphoblastic leukemia.

Detailed Description

Enroll patients after confirming eligibility. Following enrollment, peripheral blood mononuclear cells and blood plasma will be obtained from each subject by apheresis to start the manufacturing of TBI-1501.

Before TBI-1501 administration, it is necessary to pass the quality tests. Subject will be hospitalized from Day -3 to Day 28, and administered Cyclophosphamide (1,000 mg/m2/day×2 days) on Day -3 and Day -2.

Study Timeline

• Study First Submitted: 2017-04-14
• Study First Submitted QC: 2017-05-15
• Study First Posted: 2017-05-16
• Study Start: 2017-06-01
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-18
• Last Update Posted: 2024-11-20
• Primary Completion: 2035-03-31
• Study Completion: 2035-03-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

1. In phase-1 study, patients must be ≥ 18 years of age. In phase-2 study, patients must be ≥ 16 years of age.

2. Patients with relapse or refractory CD19+ acute B-cell lymphoblastic leukemia

3. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

4. Patients must have adequate key organ function (bone marrow, heart, lung, liver, renal, etc), as defined below

   • Total bilirubin level ≤1.5xULN (Upper limit of normal)
   • AST(GOT)/ALT(GPT) level ≤5.0xULN
   • Serum creatinine ≤2.0mg/dL
   • SpO2 ≧ 92%
   • LVEF ≥50%

5. Patients must be able to understand and willing to sign a written informed consent document (for patients <20 years of age their legal guardian must give informed consent).

Exclusion Criteria

1. White blood cell counts ≧ 50,000/uL
2. Received expected antitumor therapy (chemotherapy or radiation therapy, etc) within 2 weeks.
3. Received HSCT within 12 weeks before enrollment.
4. Under treatment for GVHD.
5. lymphocytes except for blasts ≦ 500/uL
6. Presence of active CNS-3
7. Concurrent use of systemic steroids or immunosuppressive agents (except for replacement therapy and local administration. e.g. inhalation, application and so on).
8. HBs Ag positive ,or either HBc Ab positive or HBs positive with HBV-DNA > 1.3LogIU/ml
9. Presence of active hepatitis C infection
10. HIV Ab or anti-HTLV-1 Ab positive
11. History of allergy about component of investigational product or animal(cattle and/or mouse)-derived additives
12. Hypersensitivity to antibiotics.
13. Presence of symptomatic cardiac arrhythmias or serious heart disease.
14. Presence of another malignant tumor.
15. Psychiatric disorder, alcohol addiction or drug addiction that affects the ability of informed consent.
16. Active or serious infection.
17. Both men and women who have generative functions, and who cannot agree with using contraceptive devices from the day of the consent to the end of study.
18. Pregnant or lactating women.
19. Any other patients judged by the investigators to be inappropriate for the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose Level -1 to 2	TBI-1501	0.3 to 3 x 10\^6 autologous CD19-CAR-T cells/kg per patient will be administered intravenously after a conditioning chemotherapy with cyclophosphamide. cohort -1: 3×10\^5 cells/kg cohort 1: 1×10\^6 cells/kg cohort 2: 3×10\^6 cells/kg.

Primary Outcome Measures

Name	Time	Method
Phase-I portion: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	One year	Adverse event (frequency, seriousness, duration, causality, severity, classification), mortality, severe adverse event, discontinuation due to adverse event.
Phase-II portion: Anti-tumor effect (CR+CRi rate)	56 days	Complete Remission (CR)+Complete Remission with Incomplete Blood Count Recovery (CRi) , as determined by assessments of peripheral blood and bone marrow.

Trial Locations

Locations (11)

The Institute of Medical Science, The University of Tokyo; 🇯🇵 Minato-ku, Tokyo, Japan

Hokkaido University Hospital; 🇯🇵 Sapporo-shi, Hokkaido, Japan

University Of Fukui Hospital; 🇯🇵 Yoshida, Fukui, Japan

Kyushu University Hospital; 🇯🇵 Higashi-ku, Fukuoka, Japan

Kobe City Medical Center General Hospital; 🇯🇵 Kobe, Hyogo, Japan

Mie University Hospital; 🇯🇵 Tsu-shi, Mie, Japan

Jichi Medical University hospital; 🇯🇵 Shimotsuke-shi, Tochigi, Japan

Tohoku University Hospital; 🇯🇵 Sendai, Miyagi, Japan

Okayama University Hospital; 🇯🇵 Okayama, Japan

Akita University Hospital; 🇯🇵 Akita, Japan

Cancer Institute Hospital Of JFCR; 🇯🇵 Kōto, Tokyo, Japan